title: Chronic administration of udenafil, a selective phosphodiesterase type 5 inhibitor, promotes erectile function recovery in an animal model of bilateral cavernous nerve crush injury.
abstract: BACKGROUND
  Preservation of the cavernous nerves (CNs) during radical prostatectomy is crucial for the patient's erectile function. Despite advances in operative technique, the majority of men report compromised erectile function postprostatectomy or complete loss of potency due to CN trauma even with nerve-sparing modifications.
  
  
  OBJECTIVE
  This study was designed to investigate whether repeated dosing of udenafil, a phosphodiesterase type 5 inhibitor, helps to improve erectile function after CN injury.
  
  
  METHODS
  Using the CN crush injury model, 8-week-old male Sprague Dawley rats were divided into the following groups; sham-operated group, bilateral CN crush injury exposed to either no udenafil (vehicle) or udenafil (5, 20 mg/kg) daily for two different durations (4 and 8 weeks, p.o.).
  
  
  METHODS
  At both time points, CN electrical stimulation was used to assess erectile function by measuring the intracavernous pressure. The expressions of hypoxia-inducible factor 1-alpha (HIF-1α), transforming growth factor-beta (TGF-β1), nerve growth factor (NGF), endothelin B receptor (ET(B) ), endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and sonic hedgehog homolog (SHH) in penile tissue were examined. Immunohistochemical antibody staining was performed for NGF, eNOS, nNOS, CD31, and alpha-smooth muscle actin (α-SMA). Additionally, terminal deoxynucleotidyl transferase-mediated nick-end labeling assay was performed to quantify apoptosis and the tissue slides were stained for Masson's trichrome to assess the smooth muscle/collagen ratio.
  
  
  RESULTS
  Udenafil improved erectile function in a dose- and time-dependent manner with the maximum erectile function recovery achieved by 20 mg/kg udenafil at an 8-week time point. CN injury increased the expression of HIF-1α, TGF-β1, NGF, and ET(B) , however, decreased the expression of eNOS, nNOS, and SHH. Udenafil significantly suppressed these alterations. The results from the histological analyses show that udenafil markedly reduces apoptosis induced by CN injury and augments the smooth muscle/collagen ratio.
  
  
  CONCLUSIONS
  CN injury induces significantly impaired erectile function and altered gene/protein expression. Chronic administration of udenafil preserves erectile function and has a beneficial role against the pathophysiological consequences of CN injury.
authors.affiliation: Dong-A Pharmaceutical Company, Giheung, Yongin, Gyeonggi, Korea.
authors.forename: Chan-Ho
authors.initials: CH
authors.lastname: Lee
authors.forename: Hae-Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: Moon-Jung
authors.initials: MJ
authors.lastname: Goo
authors.forename: Kyung-Koo
authors.initials: KK
authors.lastname: Kang
authors.forename: Byoung-Ok
authors.initials: BO
authors.lastname: Ahn
authors.forename: Soon Hoe
authors.initials: SH
authors.lastname: Kim
authors.forename: Dae-Yul
authors.initials: DY
authors.lastname: Yang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology; D053823:Hedgehog Proteins / Q000032:analysis; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis; D008297:Male; D020932:Nerve Growth Factor / Q000032:analysis; D052248:Nitric Oxide Synthase Type I / Q000032:analysis; D052250:Nitric Oxide Synthase Type III / Q000032:analysis; D010410:Penile Erection / Q000187:drug effects; D010413:Penis / Q000737:chemistry / Q000187:drug effects / Q000294:innervation; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044023:Receptor, Endothelin B / Q000032:analysis; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000032:analysis; D000096926:Benzenesulfonamides
chemical_list: D053823:Hedgehog Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D020932:Nerve Growth Factor; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D058986:Phosphodiesterase 5 Inhibitors; D011743:Pyrimidines; D044023:Receptor, Endothelin B; D013449:Sulfonamides; D053773:Transforming Growth Factor beta1; C497444:Hif1a protein, rat; C546888:Shh protein, rat; C419664:udenafil; D000096926:Benzenesulfonamides